Alfredo Nicosia
Development of genetic vaccines against infectious diseases and cancer

Alfredo Nicosia

  • Alfredo was previously a co-founder and Chief Scientific Officer of Okairos, leading preclinical and clinical development of several vaccines and monoclonal antibodies against infectious diseases and cancer.
    Alfredo’s experience includes the positions of senior director of the Viral Diseases Vaccine program at Istituto di Ricerche di Biologia Molecolare (IRBM), staff scientist at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany and project leader at the Sclavo Research Centre in Siena, Italy.
    He has published many articles in leading journals on a range of subjects, including viral and bacterial infection and vaccines.
    Alfredo holds a degree in chemistry from the University of Rome, Italy and is Professor of
    Molecular Biology at the University of Naples “Federico II”.

    Alfredo era precedentemente co-fondatore e “Chief Scientific Officer” di Okairos, leader nello sviluppo preclinico e clinico di diversi vaccini e anticorpi monoclonali contro malattie infettive e cancro.
    L'esperienza di Alfredo comprende posizioni di “Senior Director” del programma Viral Diseases Vaccine presso l'Istituto di Ricerche di Biologia Molecolare (IRBM), scienziato del laboratorio europeo di biologia molecolare (EMBL) a Heidelberg, Germania e Project leaderpresso il Centro Ricerche Sclavo a Siena, Italia.

    Ha pubblicato molti articoli su importanti riviste su una serie di argomenti, tra cui infezioni virali e batteriche e vaccini.
    Alfredo ha conseguito una laurea in chimica presso l'Università di Roma, ed è professore di biologia molecolare presso l'Università di Napoli "Federico II".

Curriculum552.84 KB

Our group develops genetic vaccines for major infectious diseases, using the highly innovative chimpanzee-derived adenovirus (ChAd) platform. Unlike the human adenoviruses which are rapidly inactivated by our immune system we have all been exposed to adenoviral infection , those of chimpanzees are not recognised by our immune system and trigger a strong response, both from the T- and the B-lymphocytes. We therefore used chimpanzees’ adenoviruses as a ‘Trojan horses’ in which we inserted pathogen-specific proteins. We proved the efficacy of our T-cell based vaccines including ChAd as a primer and Modified Vaccinia Ankara as a booster in relevant animal models. These vaccines have now been evaluated in thousands of subjects in a wide age range and were shown to be safe and highly immunogenic.
We are also expanding our research to the field of cancer vaccines encoding tumor-specific neo-antigens. We have combined the use of viral vectors that have been engineered and optimized to express artificial genes encoding high-dimensional strings of human neoantigens, with state-of-the art bioinformatics for cancer neoantigen prediction. The unprecedented neoantigen-encoding capacity of our platform and its ability to efficiently

and consistently express large numbers of neoantigens, provides significant advantages over other strategies, offering a unique approch to the potentiation of human anti-tumor immune responses.
Tumors associated with Mismatch Repair Deficiency (dMMR) and Microsatellite instability (MSI) accumulate insertion/deletion mutations (indels) that are predictable as they principally arise at mononucleotide repeats. These indel mutations in coding regions result in a translational shift that generate frame shift peptides (FSPs). FSPs are highly immunogenic and may be safely utilized in vaccines as they bear no resemblance to natural protein sequences found in the human proteome. As such, they are ideal tumor- specific neoantigens.

As these mutations are targeted to a limited number of genes across the genome, several of them are shared across different patients. MSI-associated tumors consequently offer a unique opportunity for an ‘off-the-shelf’ vaccine.
NOUS-209 encodes 209 unique FSP cancer neoantigens found in different MSI tumor types. It has the potential to be the first ‘off-the-shelf’ cancer genetic vaccine to be tested in humans.

The first-in-human NOUS-209 Phase I clinical study is scheduled to commence in early 2019.
NOUS-100-PV is a personalised cancer genetic vaccine based on patient-specific neoantigens sourced from individual patient tumor mutanomes. The technology may be applied to any cancer indication where a tumor biopsy is available that is suitable for next- generation sequencing (NGS). Our initial studies will in the first instance target tumors with high frequencies of somatic mutations, such as advanced non-small cell lung cancer (NSCLC).

We have developed a robust and rapid 5 week needle-to-needle vaccine manufacturing process from the time of patient biopsy to vaccine production. This process allows for the assembly of strings of over 60 unique patient mutanome-specific neoantigens within a single genetic vaccine vector and the production of small patient-specific quantities of personalized vaccine.

NOUS-100-PV is anticipated to enter the clinic in 2019.

Research lines
  1. Development of genetic vaccines for major infectious diseases using the highly innovative chimpanzee-derived adenovirus (ChAd) platform.
  2. Using of viral vectors that have been engineered and optimized to express artificial genes encoding high-dimensional strings of human neoantigens.
  3. Personalised cancer genetic vaccine based on patient-specific neoantigens sourced from individual patient tumor mutanomes.
Most relevant publications
  1. Colloca S., Barnes E., Folgori A., Ammendola V., Capone S., Cirillo A., Siani L., Naddeo

    M., Grazioli F., Esposito ML., Ambrosio M., Sparacino A., Bartiromo M., Meola A., Smith K., Kurioka A., O'Hara GA., Ewer KJ., Anagnostou N., Bliss C., Hill AV., Traboni C., Klenerman P., Cortese R., Nicosia A.
    Vaccine vectors derived from a large collection of simian adenoviruses induce potent cellular immunity across multiple species
    Sci Transl Med. 2012 Jan 4;4(115):115ra2

  2. Ledgerwood JE., DeZure AD., Stanley DA., Novik L., Enama ME., Berkowitz NM., Hu Z., Joshi G., Ploquin A., Sitar S., Gordon IJ., Plummer SA., Holman LA., Hendel CS., Yamshchikov G., Roman F., Nicosia A., Colloca S., Cortese R., Bailer RT., Schwartz RM., Roederer M., Mascola JR., Koup RA., Sullivan NJ., Graham BS.; the VRC 207 Study Team.

    Chimpanzee Adenovirus Vector Ebola Vaccine - Preliminary Report. N Engl J Med. 2014 Nov 2

  3. Green C.A., Scarselli E., Sande C. J, Thompson A. J., de Lara C. M., Taylor K. S., Haworth K., Del Sorbo M., Angus B., Siani L., Di Marco S., Traboni C., Folgori A., Colloca S., Capone S., Vitelli A., Cortese R., Klenerman P., Nicosia A., Pollard A. J. Chimpanzee adenovirus- and MVA-vectored respiratory syncytial virus vaccine is safe and immunogenic in adults.

    Science translational medicine, 2015 Aug 12; 7(300):300ra126. doi: 10.1126/scitranslmed.aac5745.

  4. Taylor G., Thom M., Capone S., Pierantoni A., Guzman E., Herbert R., Scarselli E., Napolitano F., Giuliani A., Folgori A., Colloca S., Cortese R., Nicosia A., Vitelli A. Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections.

    Science translational medicine, 2015 Aug 12; 7(300):300ra127. doi: 10.1126/scitranslmed.aac5757.

  5. Ewer K, Rampling T, Venkatraman N, Bowyer G, Wright D, Lambe T, Imoukhuede EB, Payne R, Fehling SK, Strecker T, Biedenkopf N, Krähling V, Tully CM, Edwards NJ, Bentley EM, Samuel D, Labbé G, Jin J, Gibani M, Minhinnick A, Wilkie M, Poulton I, Lella N, Roberts R, Hartnell F, Bliss C, Sierra-Davidson K, Powlson J, Berrie E, Tedder R, Roman F, De Ryck I, Nicosia A, Sullivan NJ, Stanley DA, Mbaya OT, Ledgerwood JE, Schwartz RM, Siani L, Colloca S, Folgori A, Di Marco S, Cortese R, Wright E, Becker S, Graham BS, Koup RA, Levine MM, Volkmann A, Chaplin P, Pollard AJ, Draper SJ, Ballou WR, Lawrie A, Gilbert SC, Hill AV.

    A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA.
    N Engl J Med. 2016 Apr 28; 374(17):1635-46. doi: 10.1056/NEJMoa1411627. Epub 2015 Jan 28.